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Synthesis, characterization, DFT study, DNA/BSA-binding affinity, and cytotoxicity of some dinuclear and trinuclear gold(III) complexes

  • Snežana Radisavljević
  • Dušan Ćoćić
  • Snežana Jovanović
  • Biljana Šmit
  • Marijana Petković
  • Nevena Milivojević
  • Nevena Planojević
  • Snežana Marković
  • Biljana PetrovićEmail author
Original Paper
  • 37 Downloads

Abstract

In this study, we have synthesized a series of dinuclear and trinuclear gold(III) complexes of the general formula [Au2(NN)Cl6] (13) for dinuclear and [Au3(NN)2Cl8]+ (46) for trinuclear compounds, respectively, in which NN is a bidentate ligand (1,4-diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane). These complexes were characterized by elemental analysis, molar conductivity, and spectroscopic techniques (IR, UV–Vis, 1H NMR, ESI–MS). We performed DFT calculations to get insight into the geometry of the studies complexes. DNA-binding studies were performed by UV–Vis spectrophotometry and fluorescence spectroscopy. The results of competitive reactions between gold(III) complexes and ethidium bromide (EB) towards DNA have shown that selected complexes can displace EB from DNA-EB adduct. In addition, these experiments confirm that polynuclear gold(III) complexes interact with DNA covalently or via intercalation. Furthermore, high values of binding constants of gold(III) complexes towards bovine serum albumin (BSA) protein indicate good binding affinity. In addition, redox stability of complexes in the presence of DNA/BSA was confirmed by cyclic voltammetry. Results of the interactions between gold(III) complexes with DNA/BSA were discussed in reference to molecular docking data obtain by Molegro virtual docker. The cytotoxic activity of synthesized gold(III) complexes was evaluated on human breast cancer cell line (MDA-MB-231), human colorectal cancer cell line (HCT-116), and normal human lung fibroblast cell line (MRC-5). All complexes dose-dependently reduced cancer and normal cells viabilities, with significant cytotoxic effects (IC50 < 25 μM) for trinuclear gold(III) complexes (4, 5) on HCT-116 cells.

Graphic abstract

Keywords

Polynuclear gold(III) complexes DFT Cytotoxicity DNA BSA Molecular docking 

Abbreviations

N–N

1,4-Diaminobutane; 1,6-diaminohexane or 1,8-diaminooctane)

CT-DNA

Calf thymus DNA

BSA

Bovine serum albumine

MDA-MB-231

Human breast cancer cell line

HTC-116

Human colon cancer cell line

MRC-5

Normal human lung fibroblast cell line

PBS

Phosphate-buffered saline

DMEM

Dulbecco’s Modified Eagle Medium

DMSO

Dimethyl sulfoxide

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide

TSP

Trimethylsilylpropanoic acid

EB

Ethidium bromide

SPSS

Statistical software package for Windows, ver. 17, 2008

IC50

Inhibitory dose which inhibit 50% growth cells

HOMO

Highest occupied molecular orbitals

LUMO

Lowest unoccupied molecular orbitals

DFT

Density functional theory

Kb

Intrinsic binding constants

Ksv

Stern–Volmer quenching constant

kq

Quenching rate constant

n

Number of binding sites per albumin

η

Viscosity of DNA in the presence of complex

η0

Viscosity of DNA alone

B3LYP

Becke, three-parameter, Lee–Yang–Parr functional

cc-pVTZ

Correlation-consistent polarized valence-only Triple-Zeta basis set

LanL2TZ

Los Alamos effective core potential triple-zeta basis set

ZPE

Zero-point vibrational energies

CPCM

Conductor-like polarizable continuum model

MVD

Molegro Virtual Docker version 2013.6.0.1

B-DNA

Crystal structure of DNA in Protein Data Bank

PDB

Protein Data Bank

4F5S

Crystal structure of BSA in Protein Data Bank

Notes

Acknowledgements

The authors gratefully acknowledge financial support of the Ministry of Education, Science and Technological Development of the Republic of Serbia (Project Nos. 172011 and III41010)

Compliance with ethical standards

Conflict of interest

There are no conflicts of interest to declare.

Supplementary material

775_2019_1716_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1165 kb)

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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  • Snežana Radisavljević
    • 1
  • Dušan Ćoćić
    • 1
  • Snežana Jovanović
    • 1
  • Biljana Šmit
    • 1
  • Marijana Petković
    • 2
  • Nevena Milivojević
    • 3
  • Nevena Planojević
    • 3
  • Snežana Marković
    • 3
  • Biljana Petrović
    • 1
    Email author
  1. 1.Department of Chemistry, Faculty of ScienceUniversity of KragujevacKragujevacSerbia
  2. 2.“Vinča” Institute of Nuclear ScienceUniversity of BelgradeBelgradeSerbia
  3. 3.Department of Biology, Faculty of ScienceUniversity of KragujevacKragujevacSerbia

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